We are searching for genetic linkage between short tandem repeat (STR) markers and genes that contribute to the predisposition to alcoholism and related behaviors. This involves development of a battery of at least 200 highly polymorphic marker loci that span the human genome at approximately 10 centimorgan intervals, or less. We are using fluorescent dye technology and constructing panels of approximately 10 loci that can be run simultaneously in one gel lane. This will facilitate fast and accurate data collection. Computer programs are being written to interface between the gel analysis machinery and statistical databases. These programs save time and reduce the potential for data entry and retrieval errors. In addition, we are developing methods for PCR-STR optimization and for precise STR allele determinations. As many genotypes have already been collected, we have begun linkage analyses using affected relative pair methods and linkage disequilibrium. The informativeness of STR markers bestows new and heretofore unattainable power for establishing, and excluding, genetic linkage between definable chromosome segments and genetic vulnerability to disease.